A new way to make chemicals not found in nature

Scientists develop a technique that expands the potential of synthetic biology

Adapted from a UC Berkeley news release.

Synthetic biologists have successfully engineered microbes to make chemicals cheaply and more sustainably. However, researchers have been limited by the fact that microbes can only make molecules using chemical reactions seen in nature.

A collaboration between scientists at Berkeley Lab and UC Berkeley has engineered the microbe E. coli to produce a molecule that, until now, could only be synthesized in a laboratory.

To achieve this outcome, the researchers integrated a specific type of modified enzyme into E. coli, along with a pathway to produce a precursor molecule. This was then converted into a novel product from a reaction not previously seen in nature.

This research opens the door to the production of a wide range of chemicals from microbes, the researchers said. Co-author Aindrila Mukhopadhyay, Berkeley Lab senior scientist in the Biosciences Area and vice president of the Biofuels and Bioproducts Division at the Joint BioEnergy Institute (JBEI) said this method could be a game changer in terms of microbial production to make pharmaceuticals, as well as sustainable fuels.

“Today, many drugs are laboriously extracted from biological systems that are challenging to cultivate or processes that negatively impact the environment. To be able to reliably make these compounds in a lab using biotechnology would really address a lot of these problems,” she said.

This applies to making “not just medicines, but precursors to polymers, renewable plastics, biofuels, building materials, the whole gamut of things that we use today, from detergents to lubricants to paints to pigments to fabric,” Mukhopadhyay added. “We really need disruptive new technologies, and this most definitely is one of them.”

In addition to Mukhopadhyay, Berkeley Lab co-authors of the study included the Biosciences Area’s Jing Huang, Douglas S. Clark, and Jay D. Keasling and the Chemical Sciences Division’s Zhennan Liu, Brandon J. Bloomer, and John F. Hartwig.

JBEI is a U.S. Department of Energy (DOE) Bioenergy Research Center led by Berkeley Lab.


New technique gets the drop on enzyme reactions

Researchers develop an efficient method for studying fast biochemical reactions as they happen in real time

By Greta Lorge

As part of an international collaboration, researchers at Berkeley Lab, the Diamond Light Source synchrotron facility, and Oxford and Bristol Universities in England have developed a novel sample delivery system that expands the limited toolkit for performing dynamic structural biology studies of enzyme catalysis, which have so far mostly been limited to a small number of light-driven enzymes.

Enzymes are molecules – primarily proteins – that tremendously accelerate biochemical reactions by selectively binding to target molecules, or substrates. Without enzymes, most biological reactions simply could not occur under temperature and pressure conditions compatible with life.

Earlier experiments have been successful in describing the time-course of these reactions, but knowledge about how the structure of the catalyst changes during the reactions has been lacking, explained Jan Kern, a staff scientist in the Biosciences Area at Berkeley Lab and one of the study’s lead authors.

The new technique builds on the team’s innovative approach of depositing microscopic dabs of crystalized enzyme slurry on a moving tape that, like a conveyor belt, carries the samples to the beam of an X-ray free-electron laser (XFEL). The researchers modified the so-called “drop on tape” design to accommodate a second nozzle to deposit a variable number of picoliter-volume (one-trillionth of a liter) droplets of substrate on top of a larger, nanoliter-volume (one-billionth of a liter) drop of enzyme microcrystal slurry.

The turbulence caused by the barrage of smaller droplets colliding with the larger one leads to rapid, even mixing so the enzyme-substrate reactions begin simultaneously throughout the sample. This makes it possible to collect serial diffraction data over a range of time, from ~100 ms to several seconds after the enzyme and substrate begin to interact to create a time-resolved “molecular movie” of the reaction cycle.

The team validated their “drop-on-drop” technique at the SACLA XFEL source in Japan using two different enzyme systems. “Our new approach allows us to follow steps of reactions in enzymes that we were not able to visualize previously. For example, we were able to see how an antibiotic drug molecule is binding to a beta lactamase, an enzyme present in antibiotic resistant bacteria that can inactivate the antibiotic,” said Kern.


Physicists snap first image of an ‘electron ice’

Breakthrough demonstrates solid state of electrons predicted more than 90 years ago

Adapted from a UC Berkeley news release.

More than 90 years ago, physicist Eugene Wigner predicted that at low densities and cold temperatures, electrons that usually zip through materials would freeze into place, forming an electron ice, or what has been dubbed a Wigner crystal.

While physicists have obtained indirect evidence that Wigner crystals exist, no one has been able to snap a picture of one – until now.

Physicists from Berkeley Lab and UC Berkeley recently published in the journal Nature an image of electron ice sandwiched between two semiconductor layers. The image is proof positive that these crystals exist.

“If you say you have an electron crystal, show me the crystal,” senior author Feng Wang, faculty senior scientist in Berkeley Lab’s Materials Sciences Division and UC Berkeley professor of physics, told Nature.

The Berkeley Lab and UC Berkeley team, involving physicists from the labs of Wang, Michael Crommie, and Alex Zettl, developed a new technique for visualizing the crystals, which tend to “melt” when probed. By placing a graphene sheet over the semiconductor sandwich, the team was able to probe the Wigner crystal with a scanning tunneling microscope without melting the sample and demonstrate the crystalline lattice structure, as Wigner predicted.

According to doctoral candidate Hongyuan Li and former postdoctoral fellow Shaowei Li, co-first authors of the paper, the study not only lays a solid foundation for understanding electron Wigner crystals, but also provides an approach that is generally applicable for imaging correlated electron lattices in other systems.


Skyrmions could be future of computing; X-ray experiments reveal their secrets

Researchers from Berkeley Lab, SLAC, Stanford, and UC San Diego show how exotic quasiparticles could have a lot in common with glass and high-temperature superconductors

Adapted from a SLAC news release.

Scientists have known for a long time that magnetism is created by the spins of electrons lining up in certain ways. But about a decade ago, they discovered another astonishing layer of complexity in magnetic materials: Under the right conditions, these spins can form skyrmions, little vortexes or whirlpools that act like particles and move around independently of the atoms that spawned them.

Because they are so stable and so tiny – about 1,000 times the size of an atom –  and are easily moved by applying small electric currents, scientists are devising ways to harness them for new types of computing and memory storage technologies that are smaller and use less energy.

In a series of recent papers, scientists from Berkeley Lab, SLAC National Accelerator Laboratory, Stanford, and UC San Diego describe experiments that suggest skyrmions can form a glass-like phase where their movements are so slow that they look like they're stuck, like cars in a traffic jam. Further, they measured how skyrmions’ natural motion with respect to each other can oscillate and change in response to an applied magnetic field, and discovered that this inherent motion never seems to entirely stop. This ever-present fluctuation suggests that skyrmions may have a lot in common with high-temperature superconductors – quantum materials whose ability to conduct electricity with no loss at relatively high temperatures may be related to fluctuating stripes of electron spin and charge.

The research team was able to observe skyrmion fluctuations in a thin magnetic film made of many alternating layers of iron and gadolinium by taking snapshots with SLAC’s Linac Coherent Light Source X-ray laser beam just 350 trillionths of a second apart. They say their method can be used to study the physics of a wide range of materials, as well as their topology – a mathematical concept that describes how an object’s shape can deform without fundamentally changing its properties. In the case of skyrmions, topology is what gives them their robust nature, making them hard to annihilate.

“I think this technique will grow and become very powerful in condensed matter physics, because there aren’t that many direct ways of measuring these fluctuations over time,” said Sujoy Roy, a staff scientist at Berkeley Lab’s Advanced Light Source. “There are a huge number of studies that can be done on things like superconductors, complex oxides and magnetic interfaces.”

Journal Link: Nature Chemistry, Oct-14-2021